Resveratrol has neuroprotective effects and plays an anti-inflammatory role through Dectin-1/p38 pathway in Aspergillus fumigatus keratitis

Weilin Diao; Min Yin; Yinghe Qi; Yudong Fu; Lingwen Gu; Jing Lin; Lina Zhang; Nan Jiang; Qian Wang; Yuwei Wang; Wendan Yi; Menghui Chi; Cui Li; Guiqiu Zhao

doi:10.1016/j.cyto.2024.156626

Resveratrol has neuroprotective effects and plays an anti-inflammatory role through Dectin-1/p38 pathway in Aspergillus fumigatus keratitis

Cytokine. 2024 Apr 27:179:156626. doi: 10.1016/j.cyto.2024.156626. Online ahead of print.

Authors

Weilin Diao¹, Min Yin¹, Yinghe Qi¹, Yudong Fu¹, Lingwen Gu¹, Jing Lin¹, Lina Zhang¹, Nan Jiang¹, Qian Wang¹, Yuwei Wang¹, Wendan Yi¹, Menghui Chi¹, Cui Li², Guiqiu Zhao³

Affiliations

¹ Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
² Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China. Electronic address: yankelicui@126.com.
³ Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China. Electronic address: zhaoguiqiu_good@126.com.

PMID: 38678810
DOI: 10.1016/j.cyto.2024.156626

Abstract

Purpose: To determine the antifungal, anti-inflammatory and neuroprotective effects of resveratrol (RES) in Aspergillus fumigatus (A. fumigatus) keratitis.

Methods: Cytotoxicity assay and Draize eye assay were performed to assess the toxicity of RES. The antifungal effect of RES was assessed by minimal inhibitory concentration, scanning or transmission electron microscopy, propidium iodide uptake assay, and Calcofluor white staining. Phosphorylation of p38 MAPK, mRNA and protein levels of Dectin-1 and related inflammatory factors were measured by qRT-PCR, ELISA and Western blot in vitro and in vivo. Clinical score, HE staining, plate count, and myeloperoxidase test were used to observe the progress of fungal keratitis. IF staining, qRT-PCR, and the Von Frey test were selected to assess the neuroprotective effects of RES.

Results: RES suppressed A. fumigatus hyphae growth and altered hyphae morphology in vitro. RES decreased the expression of Dectin-1, IL-1β and TNF-α, as well as p38 MAPK phosphorylation expression, and also decreased clinical scores, reduced inflammatory cell infiltration and neutrophil activity, and decreased fungal load. RES also protected corneal basal nerve fibers, down-regulated mechanosensitivity thresholds, and increased the mRNA levels of CGRP and TRPV-1..

Conclusion: These evidences revealed that RES could exert antifungal effects on A. fumigatus and ameliorate FK through suppressing the Dectin-1/p38 MAPK pathway to down-regulate IL-1β, IL-6, etc. expression and play protective effect on corneal nerves.

Keywords: A. fumigatus; Antifungal; Dectin-1; Keratitis; Resveratrol.